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Structural organization of HBV pgRNA genome driven by phase separation in capsid confinement
Yunqiang Bian1,2, Hai Pan1, Jiaqi Mao2,3
1Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, PR China.
Nature Communications
|February 19, 2026
Summary
Hepatitis B virus (HBV) RNA uses liquid-liquid phase separation (LLPS) to organize its genome within the capsid, forming a hollow shell. This structure enhances viral replication and offers new antiviral targets.
Area of Science:
- Virology
- Molecular Biology
- Biophysics
Background:
- Viral genome packaging into capsids is crucial for infection but poorly understood.
- Hepatitis B virus (HBV) genome organization within its capsid remains elusive.
Purpose of the Study:
- To elucidate the principles governing HBV pregenomic RNA (pgRNA) structural organization inside the capsid.
- To investigate the role of liquid-liquid phase separation (LLPS) in viral genome architecture.
Main Methods:
- Multiscale molecular dynamics (MD) simulations.
- Biochemical assays.
- Analysis of RNA-protein interactions.
Main Results:
- HBV pgRNA undergoes LLPS within the capsid, forming a hollow, shell-like condensate.
- Electrostatic interactions between pgRNA and capsid protein's C-terminal domain drive LLPS.
- LLPS creates ordered RNA microphases, balancing structural order and flexibility.
- Symmetry breaking observed at the single-particle level despite ensemble icosahedral symmetry.
- Hollow-shell architecture facilitates long-range RNA base-pairing and polymerase mobility.
Conclusions:
- Capsid-confined LLPS is a key mechanism for organizing the HBV genome.
- This organization optimizes viral genome structure and dynamics for replication.
- The discovered LLPS mechanism presents potential targets for antiviral drug development.
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